Commiphora molmol (myrrh) resin extracts and uses thereof for wound healing and treatment and prevention of mucositis and other diseases

Abstract

Provided herein are compositions comprising acidic extracts of Commiphora molmol (Myrrh) resin for the treatment and prevention of oral mucositis, mucosal infections, topical inflammations, bed sores, decubitis, inflammations of the gastrointestinal tract, canker sores, dental mouth lining ulcers, Behcet disease, and for acute and chronic wound healing. Also provided are methods for producing the disclosed compositions.

The invention claimed is: 
     
       1. A composition comprising:
 an acetic acid extract of myrrh resin of about 5% to 50% (w/w) of the composition, wherein the acetic acid extract comprises polysaccharides and sesquiterpenes, wherein the polysaccharides comprise one or more of ribofuranose, arabinopyranose, ribopyranose, uronic acid, mannopyranose, allofuronase, galacturonic acid, galactopyranose and allopyranose in a concentration of about 20% to about 40% (w/w) of the acetic acid extract, wherein the sesquiterpenes are in a concentration of about 40% to about 80% (w/w) of the acetic acid extract; 
 a hydrocolloid of about 1% to 5% (w/w) of the composition, wherein the hydrocolloid is one or more of starch, xanthan gum, guar gum, locust bean gum, gum karaya, gum tragacanth, gum Arabic, cellulose, alginate, pectin, carrageenan, gelatin, gellan and agar; and 
 a pH adjuster of about 0.1 to 1.0% (w/w) of the composition, wherein the composition has a pH in the range of about 3.0 and 5.0. 
 
     
     
       2. The composition of  claim 1 , wherein the pH adjuster is one more of ammonium bicarbonate, ammonium carbonate, ammonium citrate, ammonium hydroxide, ammonium phosphate, calcium carbonate, calcium chloride, calcium citrate, calcium fumarate, calcium hydroxide; calcium phosphate, magnesium carbonate, magnesium citrate, magnesium hydroxide, magnesium phosphate, magnesium sulfate, potassium bicarbonate, potassium carbonate, potassium citrate, potassium fumarate, potassium hydroxide, potassium sulfate, sodium bicarbonate, sodium carbonate, sodium citrate, sodium fumarate, sodium hydroxide, and sodium phosphate. 
     
     
       3. The composition of  claim 2 , the acetic acid extract of myrrh resin comprises 40-50% (w/w) furanoeudesma-1,3-dien, 10-15% (w/w) lindestrene and 5-10% (w/w) curzerene. 
     
     
       4. The composition of  claim 3 , wherein the acetic acid is in form of vinegar, and wherein the vinegar is unpasteurized and unfiltered apple cider vinegar. 
     
     
       5. The composition of  claim 4 , wherein the acetic acid extract of myrrh resin comprises myrrh resin and apple cider vinegar in a ratio of 1:4. 
     
     
       6. The composition of  claim 1 , wherein the composition comprises about 30% (w/w) of myrrh resin extract; about 3% (w/w) of xanthan gum; and about 0.5% of calcium carbonate, and wherein the composition further comprises a preservative selected from one or more of a benzoate, a nitrite, a sulphite and a sorbate. 
     
     
       7. The composition of  claim 6 , wherein the preservative is sodium benzoate. 
     
     
       8. The composition of  claim 1 , wherein the composition is a Newtonian fluid in form of a mouthwash, a cream, a gel, or a wound healing composition. 
     
     
       9. The composition of  claim 8 , wherein the mouthwash further comprises an excipient, and wherein the excipient is one or more of betaine anhydrous, glycerin, a thymol extract, a clove extract, a mint extract, a fruit flavor, and a  Stevia  powder. 
     
     
       10. The composition of  claim 9 , wherein the mouthwash comprises 2-6% (w/w) betaine anhydrous; 1-10% (w/w) glycerin; 0.01-0.1% (w/w) thymol extract; 0.5-1% (w/w) clove extract; 0.5-1% (w/w) mint extract; 0.5-1% (w/w) fruit flavor; and 0.1-0.5% (w/w)  Stevia  powder. 
     
     
       11. The composition of  claim 8 , wherein the composition is a cream having a density between about 1.059 and about 1.015 g/cm 3  and a viscosity between about 130,200 and about 166,700 centipoise at room temperature, wherein the composition further comprises an excipient in a concentration between about 10% and about 18%, and wherein the excipient is one or more of water, zinc oxide,  Hypericum  perforatum oil, cera alba, PEG-7, glyceryl cocoate, glycerin,  Prunus  amygdalus  sativa  kernel oil, ethylhexyl stearate, cetyl alcohol, coco-caprylate,  Theobroma cacao  seed butter, glyceryl stearate, allantoin, aloe barbadensis leaf juice, tocopheryl acetate, panthenol, cetearyl alcohol, hydrogenated palm kernel glycerides, hydrogenated palm glyceride, stearic acid, dicaprylyl ether, sodium lauroyl glutamate, cetearyl olivate, phenoxyethanol, ethylhexyl glycerine, and sorbitan olivate. 
     
     
       12. The composition of  claim 11 , wherein the cream comprises 5-10% (w/w) zinc oxide; 4-8% (w/w)  Hypericum  perforatum oil; 3-8% (w/w) Cera alba; 2-5% (w/w)  Prunus  amygdalus  sativa  kernel oil; 2-5% (w/w)  Theobroma cacao  seed butter; and 0.5-1.5% (w/w) allantoin. 
     
     
       13. The composition of  claim 8 , wherein the composition is a gel having a density between about 0.9185 and about 1.0521 g/cm 3  and a viscosity between about 30,900 and about 33,900 centipoise at room temperature. 
     
     
       14. A process of preparing an acidic myrrh resin extract enriched in sesquiterpenes and polysaccharides, wherein the process comprises: (1) collecting myrrh resin from  Commiphora  molmol; (2) drying the myrrh resin at a temperature between −10° C. to about −4° C. for a period of time between 24 and 72 hours; (3) dissolving the dried myrrh resin in acidic solvent to obtain a solution; (4) filtering the solution to collect an extract; (5) filtering and cooling the extract; and (6) adjusting the extract's pH to a pH range between about 3.0 and about 5.0 with a pH adjuster to obtain an acidic extract of myrrh resin enriched in sesquiterpenes and polysaccharides. 
     
     
       15. The process of  claim 14 , wherein the process further comprises (8) adding a hydrocolloid to the extract; and (9) adjusting the extract's pH to a pH range between about 3.0 and about 5.0 with a pH adjuster to obtain a composition comprising an acidic extract of myrrh resin enriched in sesquiterpenes and polysaccharides. 
     
     
       16. The process of  claim 15 , wherein the acidic solvent is vinegar, and wherein the vinegar is unpasteurized and unfiltered apple cider vinegar. 
     
     
       17. The process of  claim 16 , wherein the myrrh resin and the apple cider vinegar are in a ratio of 1:4. 
     
     
       18. The process of  claim 17 , wherein the hydrocolloid is one or more of starch, xanthan gum, guar gum, locust bean gum, gum karaya, gum tragacanth, gum Arabic, cellulose, alginate, pectin, carrageenan, gelatin, gellan and agar. 
     
     
       19. The process of  claim 18 , wherein the pH adjuster is one or more of ammonium bicarbonate, ammonium carbonate, ammonium citrate, ammonium hydroxide, ammonium phosphate, calcium carbonate, calcium chloride, calcium citrate, calcium fumarate, calcium hydroxide, calcium phosphate, magnesium carbonate, magnesium citrate, magnesium hydroxide, magnesium phosphate, magnesium sulfate, potassium bicarbonate, potassium carbonate, potassium citrate, potassium fumarate, potassium hydroxide, potassium sulfate, sodium bicarbonate, sodium carbonate, sodium citrate, sodium fumarate, sodium hydroxide, and sodium phosphate. 
     
     
       20. The process of  claim 19 , wherein the hydrocolloid is xanthan gum and the pH adjuster is calcium carbonate, and wherein the composition has a pH between about 3.5 and 4.5. 
     
     
       21. The process of  claim 20 , wherein the composition comprises about 5 to 50% (w/w) of myrrh resin extract; about 1 to about 5% (w/w) of xanthan gum; and about 0.1 to about 1.0% of calcium carbonate. 
     
     
       22. The process of  claim 21 , wherein the composition comprises about 30% (w/w) of myrrh resin extract; about 3% (w/w) of xanthan gum; and about 0.5% of calcium carbonate. 
     
     
       23. The process of  claim 22 , wherein the composition is in form of a Newtonian fluid, and wherein the process further comprises adding one or more of a preservative, an excipient or gelling agent to produce a mouthwash, a cream, a gel, a food product or a wound healing composition. 
     
     
       24. The process of  claim 23 , wherein the preservative is one or more of a benzoate, a nitrite, a sulphite and a sorbate, and wherein the excipient is one or more of betaine anhydrous, glycerin, a thymol extract, a clove extract, a mint extract, a fruit flavor, a  Stevia  powder, water, zinc oxide,  Hypericum  perforatum oil, cera alba, PEG-7, glyceryl cocoate, glycerin,  Prunus  amygdalus  sativa  kernel oil, ethylhexyl stearate, cetyl alcohol, coco-caprylate,  Theobroma cacao  seed butter, glyceryl stearate, allantoin, aloe barbadensis leaf juice, tocopheryl acetate, panthenol, cetearyl alcohol, hydrogenated palm kernel glycerides, hydrogenated palm glyceride, stearic acid, dicaprylyl ether, sodium lauroyl glutamate, cetearyl olivate, phenoxyethanol, ethylhexyl glycerine, and sorbitan olivate. 
     
     
       25. The process of  claim 24 , wherein the mouthwash comprises 2-6% (w/w) betaine anhydrous; 1-10% (w/w) glycerin; 0.01-0.1% (w/w) thymol extract; 0.5-1% (w/w) clove extract; 0.5-1% (w/w) mint extract; 0.5-1% (w/w) fruit flavor; and 0.1-0.5% (w/w)  Stevia  powder. 
     
     
       26. The process of  claim 24 , wherein the cream has a density between about 1.059 and about 1.015 g/cm 3 , and a viscosity between about 130,200 and about 166,700 centipoise at room temperature, and wherein the cream comprises 5-10% (w/w) zinc oxide; 4-8% (w/w)  Hypericum  perforatum oil; 3-8% (w/w) Cera alba; 2-5% (w/w)  Prunus  amygdalus  sativa  kernel oil; 2-5% (w/w)  Theobroma cacao  seed butter; and 0.5-1.5% (w/w) allantoin. 
     
     
       27. The process of  claim 24 , wherein the gel has a density between about 0.9185 and about 1.0521 g/cm 3 , and a viscosity between about 30,900 and about 33,900 centipoise at room temperature. 
     
     
       28. The process of  claim 24 , wherein the food product is a dairy product, a yoghurt, an ice cream, a milk-based drink, a milk-based garnish, a pudding, a milkshake, an ice tea, a fruit juice, a diet drink, a soda, a sports drink, a powdered drink mixture for dietary supplementation, an infant and baby food, a calcium-supplemented orange juice, a sauce or a soup. 
     
     
       29. A method for treating, managing or preventing oral mucositis in a subject in need thereof, wherein the method comprises topically administering to the subject's oral mucosa the composition of  claim 8 . 
     
     
       30. The method of  claim 29 , wherein the composition is in form of a mouthwash comprising 2-6% (w/w) betaine anhydrous; 1-10% (w/w) glycerin; 0.01-0.1% (w/w) thymol extract; 0.5-1% (w/w) clove extract; 0.5-1% (w/w) mint extract; 0.5-1% (w/w) fruit flavor; and 0.1-0.5% (w/w)  Stevia  powder. 
     
     
       31. The method of  claim 29 , wherein the composition is in form of a gel having a density between about 0.9185 and about 1.0521 g/cm 3 , and a viscosity between about 30,900 and about 33,900 centipoise at room temperature. 
     
     
       32. The method of  claim 29 , wherein the composition is in form of a food product, and wherein the food product is a dairy product, a yoghurt, an ice cream, a milk-based drink, a milk-based garnish, a pudding, a milkshake, an ice tea, a fruit juice, a diet drink, a soda, a sports drink, a powdered drink mixture for dietary supplementation, an infant and baby food, a calcium-supplemented orange juice, a sauce or a soup. 
     
     
       33. A method of treating, managing or preventing an inflammation, an ulcer or a wound in a subject in need thereof, wherein the method comprises administering to the subject the composition of  claim 1 . 
     
     
       34. The method of  claim 33 , wherein the ulcer is a mucosal ulcer, an oral mucosal ulcer, or a gastrointestinal ulcer. 
     
     
       35. The method of  claim 33 , wherein the inflammation is gastrointestinal mucositis, a canker sore, or Behcet disease. 
     
     
       36. The method of  claim 33 , wherein the wound is a chronic wound, an abrasion, a furuncle or a skin inflammation. 
     
     
       37. The method of  claim 33 , wherein the composition is in form of a mouthwash, and wherein the mouthwash further comprises an excipient selected from one or more of betaine anhydrous, glycerin, a thymol extract, a clove extract, a mint extract, a fruit flavor, and a  Stevia  powder. 
     
     
       38. The method of  claim 37 , wherein the mouthwash comprises 2-6% (w/w) betaine anhydrous; 1-10% (w/w) glycerin; 0.01-0.1% (w/w) thymol extract; 0.5-1% (w/w) clove extract; 0.5-1% (w/w) mint extract; 0.5-1% (w/w) fruit flavor; and 0.1-0.5% (w/w)  Stevia  powder. 
     
     
       39. The method of  claim 33 , wherein the composition is in form of a cream which further comprises an excipient in a concentration between about 10% and about 18%, and wherein the excipient is one or more of water, zinc oxide,  Hypericum  perforatum oil, cera alba, PEG-7, glyceryl cocoate, glycerin,  Prunus  amygdalus  sativa  kernel oil, ethylhexyl stearate, cetyl alcohol, coco-caprylate,  Theobroma cacao  seed butter, glyceryl stearate, allantoin, aloe barbadensis leaf juice, tocopheryl acetate, panthenol, cetearyl alcohol, hydrogenated palm kernel glycerides, hydrogenated palm glyceride, stearic acid, dicaprylyl ether, sodium lauroyl glutamate, cetearyl olivate, phenoxyethanol, ethylhexyl glycerine, and sorbitan olivate. 
     
     
       40. The method of  claim 39 , wherein the cream has a density between about 1.059 and about 1.015 g/cm 3 , and a viscosity between about 130,200 and about 166,700 centipoise at room temperature, and wherein the cream comprises 5-10% (w/w) zinc oxide; 4-8% (w/w)  Hypericum  perforatum oil; 3-8% (w/w) Cera alba; 2-5% (w/w)  Prunus  amygdalus  sativa  kernel oil; 2-5% (w/w)  Theobroma cacao  seed butter; and 0.5-1.5% (w/w) allantoin. 
     
     
       41. The method of  claim 33 , wherein the composition is in form of a gel having a density between about 0.9185 and about 1.0521 g/cm 3 , and a viscosity between about 30,900 and about 33,900 centipoise at room temperature. 
     
     
       42. The method of  claim 33 , wherein the food product is a dairy product, a yoghurt, an ice cream, a milk-based drink, a milk-based garnish, a pudding, a milkshake, an ice tea, a fruit juice, a diet drink, a soda, a sports drink, a powdered drink mixture for dietary supplementation, an infant and baby food, a calcium-supplemented orange juice, a sauce or a soup. 
     
     
       43. The method of  claim 33 , wherein the composition is administered to the subject once a day, twice a day, three times a day, or four times a day, in a therapeutically effective amount from about 350 mg to about 600 mg/day. 
     
     
       44. The method of  claim 43 , wherein the subject is a mammal. 
     
     
       45. The method of  claim 44 , wherein the subject is a human subject. 
     
     
       46. The method of  claim 45 , wherein the composition is administered to the subject prior to, during or after exposure to radiation or chemotherapy. 
     
     
       47. A method of treating, managing or preventing a topical inflammation in a subject in need thereof, wherein the method comprises administering to the subject the composition of  claim 8 . 
     
     
       48. The method of  claim 47 , wherein the topical inflammation is a bed sore, decubitis or an acute or chronic wound inflammation. 
     
     
       49. The method of  claim 48 , wherein the composition is in form of a cream which further comprises an excipient in a concentration between about 10% and about 18%, and wherein the excipient is one or more of water, zinc oxide,  Hypericum  perforatum oil, cera alba, PEG-7, glyceryl cocoate, glycerin,  Prunus  amygdalus  sativa  kernel oil, ethylhexyl stearate, cetyl alcohol, coco-caprylate,  Theobroma cacao  seed butter, glyceryl stearate, allantoin, aloe barbadensis leaf juice, tocopheryl acetate, panthenol, cetearyl alcohol, hydrogenated palm kernel glycerides, hydrogenated palm glyceride, stearic acid, dicaprylyl ether, sodium lauroyl glutamate, cetearyl olivate, phenoxyethanol, ethylhexyl glycerine, and sorbitan olivate. 
     
     
       50. The method of  claim 49 , wherein the cream has a density between about 1.059 and about 1.015 g/cm 3 , and a viscosity between about 130,200 and about 166,700 centipoise at room temperature, and wherein the cream comprises 5-10% (w/w) zinc oxide; 4-8% (w/w)  Hypericum  perforatum oil; 3-8% (w/w) Cera alba; 2-5% (w/w)  Prunus  amygdalus  sativa  kernel oil; 2-5% (w/w)  Theobroma cacao  seed butter; and 0.5-1.5% (w/w) allantoin. 
     
     
       51. The method of  claim 48 , wherein the composition is in form of a gel having a density between about 0.9185 and about 1.0521 g/cm 3 , and a viscosity between about 30,900 and about 33,900 centipoise at room temperature. 
     
     
       52. The method of  claim 48 , wherein the composition is administered to the subject once a day, twice a day, three times a day, or four times a day, in a therapeutically effective amount. 
     
     
       53. The method of  claim 52 , wherein the subject is a mammal. 
     
     
       54. The method of  claim 53 , wherein the subject is a human subject. 
     
     
       55. The method of  claim 54 , wherein the composition is administered to the subject prior to, during or after exposure to radiation or chemotherapy.